1. Field of the Invention
The present invention relates to a method of controlling the concentration of calcium in the serum of warm-blooded animals. More particularly, the invention is concerned with a method of controlling the calcium level in the serum of warm-blooded animals by administering 25-hydroxyvitamin D.sub.3 -26,23-lactones to them and a pharmaceutical composition comprising 25-hydroxyvitamin D.sub.3 -26,23-lactones for controlling the concentration of calcium in the serum of a warm-blooded animal and a pharmaceutically acceptable carrier.
2. Description of the Prior Art
1.alpha.,25-dihydroxycholecalciferol, 1.alpha.-hydroxycholecalciferol, 1.alpha.,24-dihydroxycholecalciferol, and the like, for instance, have hitherto been known as useful compounds for the treatment of osteoporosis, osteomalacia, etc. However, these compounds incur possibility of causing ill effects such as hyper-calsemia etc., when administered in large doses.
Calcitonin is known as a drug for the treatment of hypercalsemia, etc., but it has a demerit of being not administrable orally.
Meanwhile, 1.alpha.,25-dihydroxyvitamin D.sub.3 -26,23-lactone has recently been isolated from the serum of rats and chemically identified as a novel metabolite of 1.alpha.-hydroxyvitamin D.sub.3 or 1.alpha.,25-dihydroxyvitamin D.sub.3 (Arch. Biochem. Biophs. 204, pp. 387-391, 1980; FEBS LETTERS, 134, pp. 207-211, 1981).
Also 25-hydroxyvitamin D.sub.3 -26,23-lactone was isolated from the serum of chickens, rats or pigs and identified as such (Biochemistry, 18, pp. 4775-4780, 1979; Biochemical and Biophysical Research Communication, 89, pp. 286-293, 1979; Biochemical and Biophysical Research Communication, 93, pp. 149-154, 1980).
In reference to reports on the biological activity of said 25-hydroxyvitamin D.sub.3 -26,23-lactone, International Publication Number WO 81/500045 discloses that rats which had been fed with a vitamin D.sub.3 deficient diet were given 25-hydroxy-vitamin D.sub.3 -26,23-lactone. The measurement of concentration of calcium contained in the serum made 12 hours after the administration showed that 25-hydroxyvitamin D.sub.3 -26,23-lactone increased the concentration of calcium in the serum and that accordingly "it has the activity similar to vitamin D in promoting the bone calcium mobilization."
With regard to 1.alpha.,25-dihydroxyvitamin D.sub.3 -26,23-lactone, no literature has yet been published to report on its biological activity based on the concrete pharmacological data.